A second-generation autologous chondrocyte implantation approach to the treatment of focal articular cartilage defects

Autologous chondrocyte implantation (ACI) is the most widely used cell-based surgical procedure for the repair of articular cartilage defects. Challenges to successful ACI outcomes include limitation in defect size and geometry as well as inefficient cell retention. Second-generation ACI procedures have thus focused on developing three-dimensional constructs using native and synthetic biomaterials. Clinically significant and satisfactory results from applying autologous chondrocytes seeded in fibrin within a biodegradable polymeric material were recently reported. In the future, third-generation cell-based articular cartilage repair should focus on the use of chondroprogenitor cells and biofunctionalized biomaterials for more extensive and permanent repair

Lizard tail regeneration: regulation of two distinct cartilage regions by Indian hedgehog

AbstractLizards capable of caudal autotomy exhibit the remarkable ability to “drop” and then regenerate their tails. However, the regenerated lizard tail (RLT) is known as an “imperfect replicate” due to several key anatomical differences compared to the original tail. Most striking of these “imperfections” concerns the skeleton; instead of the vertebrae of the original tail, the skeleton of the RLT takes the form of an unsegmented cartilage tube (CT). Here we have performed the first detailed staging of skeletal development of the RLT CT, identifying two distinct mineralization events. CTs isolated from RLTs of various ages were analyzed by micro-computed tomography to characterize mineralization, and to correlate skeletal development with expression of endochondral ossification markers evaluated by histology and immunohistochemistry. During early tail regeneration, shortly after CT formation, the extreme proximal CT in direct contact with the most terminal vertebra of the original tail develops a growth plate-like region that undergoes endochondral ossification. Proximal CT chondrocytes enlarge, express hypertrophic markers, including Indian hedgehog (Ihh), apoptose, and are replaced by bone. During later stages of tail regeneration, the distal CT mineralizes without endochondral ossification. The sub-perichondrium of the distal CT expresses Ihh, and the perichondrium directly calcifies without cartilage growth plate formation. The calcified CT perichondrium also contains a population of stem/progenitor cells that forms new cartilage in response to TGF-β stimulation. Treatment with the Ihh inhibitor cyclopamine inhibited both proximal CT ossification and distal CT calcification. Thus, while the two mineralization events are spatially, temporally, and mechanistically very different, they both involve Ihh. Taken together, these results suggest that Ihh regulates CT mineralization during two distinct stages of lizard tail regeneration

Adult stem cell-based therapy for degenerative joint diseases

Cell-based therapy for regenerative medicine is a major field of biomedical research including its use in the treatment of degenerative joint disease. The goal of regenerative medicine is to develop methods to repair, replace, and regenerate diseased, injured, or non-functional tissues. Towards this goal, stem or progenitor cells have been considered a highly desirable candidate cell type, because of their expandability and potential to be induced toward specific cell differentiation lineages. A key requirement in musculoskeletal tissue engineering and regeneration is that ultimately the "regenerate tissue" needs to be a three-dimensional structure. This may be accomplished through the use of engineered constructs derived by cell seeding into natural or synthetic biomaterial scaffolds. While direct cell injection is the most convenient means of cell delivery, a scaffold-based approach is capable of producing three-dimensional engineered tissues with mechanical properties compatible with those of various musculoskeletal tissues. Of the 40-50 million Americans with osteoarthritis (OA), an estimated 10-12% suffer from post-traumatic OA. We have developed an impact model for the development of post-traumatic OA. Data on the characteristics of this model in vitro and in vivo will be presented. Focal lesions developed in vivo resulting from these traumatic impacts will be repaired using stem cell-laden hydrogel or nanofiber constructs. Concurrently, cell-hydrogel and cell-nanofibrous constructs are currently being developed for the engineering of cartilaginous tissues, and information on the fabrication and biological attributes of these various tissue-engineered composites will be presented. In conclusion, tissue engineering and regenerative medicine presents an exciting, emerging inter-disciplinary research field that is a natural platform for life scientists, engineers, and clinicians working together to develop therapeutic solutions for diseased or injured tissue and organs

Stem Cell Research & Therapy marks its first anniversary

Just over a year ago we launched Stem Cell Research & Therapy with the aim of it becoming the major forum for translational research into stem cell therapies [1]. As we celebrate our first year of publication we look back at what we have achieved and how we hope to progress in our second year and beyond. Stem Cell Research & Therapy is an international, peer-reviewed, open access journal with a special emphasis on basic, translational, and clinical research into stem cell therapeutics, including animal models, and clinical trials. At launch we noted both the enormous potential of stem cell therapies and the major hurdles that have to be overcome [1]. While the past year has seen continued legal turmoil regarding government funding of embryonic stem cell research in the USA [2], stem cell research continues to progress apace internationally.Not SpecifiedDeposited by bulk impor

Nascent osteoblast matrix inhibits osteogenesis of human mesenchymal stem cells in vitro

Introduction\ud Adult mesenchymal stem cells (MSCs) are considered promising candidates for cell-based therapies. Their potential utility derives primarily from their immunomodulatory activity, multi-lineage differentiation potential, and likely progenitor cell function in wound healing and repair of connective tissues. However, in vitro, MSCs often senesce and spontaneously differentiate into osteoblasts after prolonged expansion, likely because of lack of regulatory microenvironmental signals. In vivo, osteoblasts that line the endosteal bone marrow surface are in close proximity to MSCs in the marrow stroma and thus may help to regulate MSC fate.\ud \ud Methods\ud We examined here how osteogenic differentiation of MSCs in vitro is affected by exposure to osteoblastic cells (OBCs). Human bone marrow MSCs were exposed to OBCs, derived by induced osteogenic differentiation of MSCs, either directly in contact co-cultures, or indirectly to OBC-conditioned medium or decellularized OBC extracellular matrix (ECM).\ud \ud Results\ud Our results showed that OBCs can act as negative regulators of MSC osteogenesis. mRNA expression profiling revealed that OBCs did not affect MSC osteogenesis in direct contact cultures or via secreted factors. However, seeding MSCs on decellularized OBC ECM significantly decreased expression of several osteogenic genes and maintained their fibroblastic morphologies. Proteomic analysis identified some of the candidate protein regulators of MSC osteogenesis.\ud \ud Conclusions\ud These findings provide the basis for future studies to elucidate the signaling mechanisms responsible for osteoblast matrix-mediated regulation of MSC osteogenesis and to better manipulate MSC fate in vitro to minimize their spontaneous differentiation

Origin and Characterization of Multipotential Mesenchymal Stem Cells Derived from Adult Human Trabecular Bone

Much of the knowledge regarding the regulatory pathways for adult stem cell self-renewal and differentiation has been obtained from the results of in vitro cultures. However, it is unclear if adult stem cells are controlled in the same way under physiological conditions. We examined this issue with respect to the migration of stem cells to tissue injury and how switch from a migratory state to one of proliferation wherein they participate in development. Building on our previous identification of multipotent stem cells in trabecular bone, we have examined the in vitro behavior of these cells within the bone milieu. We found that cell proliferation is inhibited within the trabecular bone niche as cells migrate out of the trabecular bone prior to proliferation. Additionally, multiple cell types were detected in adult trabecular bone, including osteoblasts, osteoclasts, endothelial cells, and Stro-1-positive mesenchymal stem cells. Furthermore, we demonstrated that Stro-1-positive cells migrated out of their native bone niche to generate multipotential stem and progenitor cells during in vitro culture. We conclude that self-renewal and differentiation of adult stem cells in connective tissues are tightly controlled and separately orchestrated processes. A regulatory network of extrinsic factors and intrinsic signals acts to stimulate the exit of stem cells from their niche so that they can localize to sites of wound healing, where they participate in development after functional differentiation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63409/1/scd.2005.14.712.pd